Methylmalonate Semialdehyde Dehydrogenase Deficiency

What else is it called?


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What causes it?

MMSDHD is an autosomal recessive condition caused by a mutation in the ALDH6A1 gene. This gene is thought to provide the body with instructions to make an enzyme which is involved in oxidoreductase activity [transferring elections]. Which essentially plays a role in the metabolism of the amino acid valine and pyrimidine metabolism. It is also thought to play a further role in the body’s metabolism by binding a molecule called fatty acyl-CoA which is essential for the energy production pathway.

With this condition, there may be failure to produce or only partially produce some of the products that are involved in the amino acid’s metabolism and the body’s energy production which can have a range of health consequences for your child.

How common is it?

At this time, due to the rarity of this condition it is difficult to quantify the number of people this condition has affected or the population it is more common within. We cannot also be certain if this metabolic condition is more common in males or females.

What are the signs and symptoms?

Signs and symptoms of this condition may present from birth. These may differ per individual however these are some of the most common ones that your child may experience with this condition:

  • Global developmental delay
  • Hypotonia
  • Small head circumference
  • Microcephaly
  • Abnormality of the digestive system
  • Abnormality of the eye
  • Dysmorphic facial features

How is it diagnosed?

This condition may be diagnosed by a urine sample to check the levels of metabolites present within the body. Previous Laboratory studies typically show increased urinary 3-hydroxyisobutyric acid, although additional metabolic abnormalities may also be observed with this condition. A child may be asymptomatic; however, they can be identified through the Newborn screening.

Newborn screening may also be available for your child depending on the country you live in. Your newborn baby will be offered some screening tests in their first 6 to 8 weeks. When your baby is about 5 days old, a midwife will collect the blood sample by pricking your baby’s heel and squeezing out a few drops of blood onto a blood spot card. This is then sent off for testing. The heel prick may be uncomfortable, and your baby may cry, but it’s all over very quickly. This is to test for potential metabolic conditions.

Can it be treated?

Previous literature has found an individual to make progress in physical development on a low protein diet valine-restricted diet. Other efforts of treatment are aimed at managing the symptoms as they present, due to the rare nature of this condition there is currently limited information on the treatment of MMSDH deficiency.

Do my family need to be tested?

MMSDHD can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inheritedMMSDHD. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

If you have previously had a child with MMSDHD and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.

Relevant Organisations


References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing [Resource Library No: AAP002].

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